FDA Accepts Supplemental NDA for Ceftazidime and Avibactam

The US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) that seeks to expand the label for ceftazidime and avibactam (AVYCAZ) to include the treatment of complicated urinary tract infections (cUTI) and complicated intraabdominal infections (cIAI) in combination with metronidazole, in children aged 3 months to 17 years.

"AVYCAZ has helped address the critical public health threat caused by difficult-to-treat gram-negative pathogens," David Nicholson, PhD, chief research & development officer at Allergan, said in a statement. "This sNDA filing acceptance is an important step towards expanding the availability of a potential treatment option to pediatric patients in need with cIAI and cUTI, including those infections caused by antibiotic-resistant pathogens."

The sNDA is based on the results of 2 active-controlled clinical studies evaluating pediatric patients and a single-dose pharmacokinetic study. The safety and efficacy of ceftazidime and avibactam were compared with meropenem in the cIAI study and cefepime in the cUTI study.

Findings from both studies were reported to be similar to findings in adult populations. Additionally, no new safety concerns were observed. Efficacy was also consistent with previous trials conducted in adults and “favorable clinical and microbiological responses were both observed against the predominant cIAI and cUTI pathogens” according to the statement.

Ceftazidime/avibactam is a fixed-dose combination antibacterial. Avibactam is a non-beta-lactam beta-lactamase inhibitor which protects ceftazidime from degradation by some beta-lactamases. Avibactam does not decrease the activity of ceftazidime against ceftazidime-susceptible organisms. Ceftazidime is a third-generation cephalosporin with a well-established efficacy and safety profile.

Ceftazidime/avibactam was approved by the FDA in February 2015, in adults 18 and older for the treatment of cUTI and cIAI (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa.

Furthermore, in February 2018, ceftazidime/avibactam was approved for the treatment of hospital-acquired pneumonia and ventilator-acquired pneumonia in adults over 18 caused by K pneumoniae, E cloacae , E coli, Serratia marcescens, Proteus mirabilis, P aeruginosa, and Haemophilus influenzae.

As Contagion^® previously reported, studies have shown a “susceptibility rate of 94.6% and an MIC₉₀ of 8 μg/mL against P aeruginosa isolates for AVYCAZ, [as well as] susceptibility to 99.9% of K pneumoniae isolates overall (MIC₉₀ .5 μg/mL) and extended spectrum beta-lactamase-producing K pneumoniae isolates (MIC₉₀ 2 μg/mL), 99.7% of all Enterobactercloacae isolates (MIC₉₀ 1 μg/mL), and 92.0% of ertapenem-resistant Enterobactercloacae isolates (MIC₉₀ 8 μg/mL).”

Ceftazidime and avibactam is being jointly developed by Allergan and Pfizer.